We are studying the aromatic amino acid hydroxylases and nitric oxide synthase (which require tetrahydrobiopterin) and the enzymes responsible fo the synthesis of tetrahydrobiopterin through an integrated interdisciplinar approach. This multi-level research is uncovering protein, substrate, effector, and product interactions that are significant in normal and diseased state biology. A central element to our research is the directed mutagenesis of the cloned enzymes to elucidate the structures and specific roles of a variety of catalytic and regulatory sites.